Advances in PSC, NAFLD, and Liver Transplantation for Patients with HCV Infection reported at International Liver Congress

A chemical cousin of an existing drug shows promise for patients with primary sclerosing cholangitis (PSC), a larger waistline increases risk for severe nonalcoholic fatty liver disease (NAFLD), and livers from hepatitis C virus (HCV)-infected donors are safe for transplant into HCV-infected recipients were all among the exciting findings reported during the annual International Liver Congress in Barcelona, Spain, April 2016.

—Michael Trauner (Medical University Vienna in Austria) reported findings from a phase 2 trial indicating that a variant of 24-norursodeoxycholic acid (norUDCA) can reduce liver damage in patients with PSC.

In PSC, which affects about 15 per 100,000 people, fibrotic obstruction of the bile ducts lead to cirrhosis and liver cancer. Patients generally are diagnosed with the disease in their 20s and 30s. There is no effective medical treatment.

norUDCA was derived by removing a side chain from the secondary bile acid UDCA. Trauner et al have previously shown in a mouse model of PSC that norUDCA increased the hydrophilicity of biliary bile acids, stimulated bile flow with flushing of injured bile ducts, and induced detoxification and elimination routes for bile acids.

MedPage Today reported findings from a trial of 161 patients from 12 countries who were either UDCA-naïve or underwent an 8-week washout before beginning the trial. None of the patients took UDCA during the 12 weeks of therapy.

Patients were randomly assigned to groups given placebo or 500, 1000, or 1500 mg each day, Trauner said. Patients were followed for an additional 4 weeks after the end of treatment.

Trauner et al found that norUDCA significantly reduced serum levels of alkaline phosphatase, compared with placebo, in a dose-dependent manner (by 12.3%, 17.3%, and 26%, respectively). The pattern was similar for other laboratory values, he said.

Based on that data, the 1500-mg dose will be tested in a phase 3 trial, Trauner said.

Trauner said that researchers measured quality of life and found no change, possibly because of the short study period. However, 80% of patients receiving placebo reported at least one adverse event, compared with 59%, 73%, and 67% of those getting the 500 mg, 1000 mg, or 1500 mg dose of norUDCA.

—Lean NAFLD with central visceral obesity is a more dangerous condition than overweight NAFLD without visceral obesity, reported Rosa Lombardi (University of Milan)

Findings from her study support the existence of lean fatty liver disease, which might be associated with a worse metabolic and liver profile than the more widely recognized obesity-related fatty liver disease, Lombardi told Medscape Medical News.

Lombardi suggests that all patients have their waist circumference measured—even if they have a normal body mass index. If the waistline has increased and other metabolic features, such as diabetes, hypertension, dyslipidemia, and insulin resistance, are present, they need to be screened for NAFLD.

The retrospective analysis included 334 patients with biopsy-proven NAFLD; 61 were normal weight (BMI < 25 kg/m²) and the rest were overweight.

In the normal-weight patients, indications for liver biopsy were persistently altered liver function tests, hyperferritinemia, and/or a long history of steatosis, especially if associated with diabetes.

The researchers used carotid intima media thickness and plaques, detected by ultrasound, to assess vascular damage. They performed liver biopsy analyses to evaluate fibrosis.

At baseline, waist circumference was larger in overweight than in normal-weight patients (104.1 vs 89.9 cm).

Lombardi reported that among the 61 patients with a BMI in the normal range, nearly 36% had nonalcoholic steatohepatitis and 20% had significant (grade 2 or higher) fibrosis.

Regardless of BMI, those with larger waistlines had worse metabolic, vascular, and liver profiles than those with smaller waistlines.

Although waist circumference often correlates with BMI, 24 patients with a BMI in the normal range had an increased waist circumference (more than 80 cm for women and 94 cm for men).

Lombardi says that the sample was small, so the data cannot be considered conclusive. But the authors observed a trend that associated lean fatty liver disease with a higher prevalence of metabolic syndrome and severe liver fibrosis, compared to patients with obesity-associated fatty liver disease.

—Over the past 2 decades, the number of HCV-positive livers transplanted has tripled. However, the medium to long-term outcomes of HCV-positive liver transplant recipients transplanted from HCV-positive donors were not different from those who received HCV-negative organs, reported Zobair Younossi.

The shortage of organs for liver transplantation has led to the use HCV-positive livers for HCV-positive recipients. Younossi et al evaluated long-term outcomes of recipients of HCV-positive livers, selecting all adults from the Scientific Registry of Transplant Recipients who were infected with HCV and underwent liver transplantation from 1995 through 2013.

They found that the proportion of HCV-positive livers transplanted gradually increased from 2.9% in 1995 to 3.3% in 2000 to 5.8% in 2005 to 6.8% in 2010 to 9.4% in 2013.

A higher proportion of patients who received livers from HCV-positive donors were alive and discharged after the procedure (95.4% vs 93.9% for HCV-negative donors), but this difference could be accounted for by the greater proportion of HCV-positive donors in more recent study years.

After transplantation, mortality for patients receiving livers from HCV-positive donors (12.5% in 1 year, 24.2% in 3 years, 33.0% in 5 years, 47.5% in 10 years) and proportions with graft loss (2.2% in 1 year, 4.8% in 3 years, 7.5% in 5 years, 13.9% in 10 years) were similar to those of patients receiving livers from HCV-negative donors.

There was no association between donor HCV status and time to post-transplant death or time to graft loss in a proportion hazard survival analysis after adjustment for the year of transplantation.

The finding, important because number of such cases has been, increasing should be a comfort to doctors and patients, especially in an era when HCV can be cured in most cases post-transplant, Younossi told MedPage Today

But Younossi cautioned it would be a mistake to think that HCV-positive organs could be safely transplanted into a patient who was not already infected, because of the risk of causing hepatitis in a person with an immune system suppressed by anti-rejection drugs.

The study is part of a widening interest in how to implement HCV care now that there are highly effective treatments.

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About the Author

Dr. Kristine Novak is the science editor for Gastroenterology and Clinical Gastroenterology and Hepatology. She has worked as an editor at biomedical research journals and as a science writer for 15 years, covering advances in gastroenterology, hepatology, cancer, immunology, biotechnology, molecular genetics, and clinical trials. She has a PhD in cell biology and an interest in all areas of medical research.